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Impact of Diabetes, Drug-Induced Liver Injury, and Sepsis on Outcomes in Metabolic Dysfunction Associated Fatty Liver Disease-Related Acute-on-Chronic Liver Failure
No full textINTRODUCTION:The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and its complication, MAFLD-related acute-on-chronic liver failure (MAFLD-ACLF), is rising. Yet, factors determining patient outcomes in MAFLD-ACLF remain understudied.METHODS:Patients with MAFLD-ACLF were recruited from the Asian Pacific Association for the Study of the Liver-ACLF Research Consortium (AARC registry). The diagnosis of MAFLD-ACLF was made when the treating unit had identified the etiology of chronic liver disease as MAFLD (or previous nomenclature such as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, or non-alcoholic steatohepatitis-cirrhosis). Patients with coexisting other etiologies of chronic liver disease (such as alcohol, hepatitis B virus, hepatitis C virus, etc.) were excluded. Data were randomly split into derivation (n = 258) and validation (n = 111) cohorts at a 70:30 ratio. The primary outcome was 90-day mortality. Only the baseline clinical, laboratory features and severity scores were considered.RESULTS:The derivation group had 258 patients; 60% were male, with a mean age of 53. Diabetes was noted in 27% and hypertension in 29%. The dominant precipitants included viral hepatitis (hepatitis A virus and hepatitis E virus, 32%), drug-induced injury (drug-induced liver injury, 29%), and sepsis (23%). Model for End-Stage Liver Disease-Sodium (MELD-Na) and AARC scores on admission averaged 32 ± 6 and 10.4 ± 1.9. At 90 days, 51% survived. Nonviral precipitant, diabetes, bilirubin, international normalized ratio, and encephalopathy were independent factors influencing mortality. Adding diabetes and precipitant to MELD-Na and AARC scores, the novel MAFLD-MELD-Na score (+12 for diabetes, +12 for nonviral precipitant), and MAFLD-AARC score (+5 for each) were formed. These outperformed the standard scores in both cohorts.DISCUSSION:Almost half of patients with MAFLD-ACLF die within 90 days. Diabetes and nonviral precipitants such as drug-induced liver injury and sepsis lead to adverse outcomes. The new MAFLD-MELD-Na and MAFLD-AARC scores provide reliable 90-day mortality predictions for patients with MAFLD-ACLF
An Automated Micro‐Immunobeads‐Based Electromagnetic Operation System (MEMOs) for Blood Testing of Alzheimer's Disease
Full text linkThe anticipated rise in the prevalence of Alzheimer's disease (AD) under global demographic shifts necessitates the development of universally accessible screening and diagnostic tools, of which blood tests hold the promise. However, the widespread adoption of blood tests remains impeded by the lack of analytically validated biomarkers and accessible decentralized platforms. Here, the study presents a portable and automated micro-immunobeads-based electromagnetic operation system, termed MEMOs, targeting potential AD blood biomarker exosome-bound Aβ42 (Exo-Aβ42), for automated blood testing of AD. MEMOs integrates a microfluidic exosome-detection biological chip (μ-Exo Biochip) embedded with a magnetic field-responsive assay for detecting Exo-Aβ42 and a microbead operation electromagnetic chip (μ-Bead EMchip) for programmable and addressable actuation, collectively delivering a high level of accurate and automated AD testing. In both animal and clinical samples, the levels of Exo-Aβ42 measured using MEMOs have shown significant correlations with various progressive stages of AD. With the features of cost-effective manufacturing, minimized hands-on time, and an easy operation workflow, MEMOs offers an accessible pathway toward diagnosing and monitoring the progression of AD in decentralized practice.preprin
Subduction-driven mantle melting controls the magmatic evolution of the early Permian Tianshan orogen
No full textMantle-derived magmas provide a window into deep geodynamic processes and the evolution of continental lithosphere. Late Paleozoic overlap of mantle plume activity beneath the Tarim craton and collisional orogenesis in the adjacent Tianshan orogen presents a rare opportunity to explore their interplay during convergent tectonics. Here, we present a comprehensive dataset on mafic dykes from the eastern Tianshan, Central Asia. Zircon U-Pb dating indicates that these dykes were emplaced at ca. 293 Ma, contemporaneous with the early eruption of the Tarim large igneous province (LIP; ca. 290 Ma). However, their arc-like major and trace element signatures point to water-fluxed melting in the mantle source, rather than melting induced by plume-related heating and decompression. Trace element modeling suggests an equivalent degree of partial melting, which could account for the formation of both the dykes and the LIP-related basalts, but this does not explain their distinct geochemical compositions. Zircon H2O contents (102–1190 ppm) from mafic dykes demonstrate a hydrous lithospheric mantle origin, contrasting with the characteristics of typical plume magmatism. Furthermore, elevated zircon εHf(t) and δ18O values (1.5–11.0 and 5.0–7.9 ‰, respectively) reveal a juvenile lithospheric mantle source with contributions from fluids derived from a subducted slab. These findings support a model involving melting within subduction-modified lithospheric mantle triggered by slab break-off, demonstrating that the Tarim plume head had minimal influence on the Tianshan orogen during the early Permian. Such processes are consistent with the spatial and temporal distribution of post-collisional mafic magmas throughout Earth's orogenic cycles. Although often overlooked due to limited surface exposure, these magmas provide stable, incremental additions to the continental lithosphere and are key drivers of long-term crustal growth.</p
Development and Validation of Mortality Prediction Models among Frail Participants in the UK Biobank Study
No full textBackgroundIdentifying effective risk assessment strategies and prediction models for frail populations is crucial for precise mortality risk identification and improved patient management. This study aimed to evaluate whether prediction models incorporating survey data combined with biomarkers, physical measurements, or both could enhance mortality risk prediction in frail individuals than survey-only models.Methods15 754 frail participants aged 40–72 from the UK Biobank were included. We used Cox models to assess all-cause mortality risk and Light Gradient Boosting Machines for variable selection by sex. Performance was evaluated through discrimination, calibration, and reclassification.ResultsIn the survey-only models, we selected 24 predictors for males and 19 for females; age and number of treatments were the top predictors for both sexes. In the biomarker models, we selected 15 predictors for males and 24 for females. In the physical measurement models, we retained 24 predictors for males and 23 for females. The base models showed good discrimination: C-statistic was 0.73 (95% CI, 0.72–0.75) for males and 0.74 (95% CI, 0.72–0.76) for females in development, and 0.70 (95% CI, 0.65–0.75) for males and 0.78 (95% CI, 0.73–0.83) for females in validation. Although incorporating additional predictors led to some improvement in model performance, the overall enhancement was not substantial.ConclusionsSurvey-based models predicted mortality in frail individuals effectively, with only minor improvements from adding biomarkers or physical measurements. These findings highlighted the value of surveys in forecasting outcomes and informed personalized management strategies to improve health for the frail.</p
Exploring the effects of technology-supported collaborative inquiry and students’ ICT competency on scientific literacy and subject knowledge in rural science classrooms
Full text linkTechnology-supported collaborative inquiry has notable potential to enhance students’ scientific literacy and subject knowledge. However, most technological supports have been conducted in non-rural science classrooms, with their effectiveness in rural classrooms remaining underexplored. Rural students exhibit varying levels of Information and Communication Technology (ICT) competency, and the impact on technology-supported science classrooms warrants further exploration. To address these gaps, this study adopted a six-week experiment to conduct technology-supported collaborative inquiry activities in two eighth-grade classes, with a total of 101 students at a rural secondary school in China. Using a 2 × 2 quasi-experiment design, this study investigated the effects of different experimental interventions and levels of ICT competency on students’ scientific literacy and subject knowledge. Students in the experiment class (n = 48) used a structured collaborative inquiry platform, i.e., WeInquiry, to conduct, record, and share their learning progress, while the students in the comparison class (n = 53) completed the same activities without the platform support. The results showed that technology-supported collaborative inquiry and students’ ICT competency were both conducive to promoting rural students’ scientific literacy. Further, the interactive effects of the experimental interventions and students’ ICT competency significantly influenced their scientific literacy and subject knowledge. The findings suggest that considering different ICT competencies, technology-supported collaborative inquiry activities can positively impact students’ science learning in rural classrooms. More studies are needed to explore how to integrate technological tools to better support science education in rural classrooms, with a particular focus on the influences of students’ ICT competencies.published_or_final_versio
Understanding the Binding and Structures in Model Complexes of Polypeptides and Cofactors
No full textCompetitive binding between metal cofactors and functional groups of polypeptides results in a diversity of structures and chemistries in metalloproteins. Herein, we examined elements of this competitive binding using [metal(auxiliary ligand)(peptide)] complexes, where the metal(auxiliary ligand) combinations are CuII(terpy)2+, CoIII(salen)+, and FeIII(salen)+ and the peptides are either the dipeptide arginine-tyrosine (RY) or the tripeptide arginine-tyrosine-glycine (RYG). Structural diversity was established and substantiated via tandem mass spectrometry, with and without peptide derivatization and substitution. All the complexes dissociated to give high abundances of the peptide radical cations, but the structures of these ions differ depending on the composition of the preceding metal complex. Density functional theory calculations provided insights into different binding modes within the complexes and also provided details of the mechanisms by which different [RY]•+ and [RYG]•+ ions fragment. Infrared multiple-photon dissociation spectroscopy established that [Cu(terpy)RYG]2+ is bound through the carboxylate group, but calculations showed that it can convert to the phenolate-bound structure under a low-energy barrier. Despite the variety and apparent complexity in binding, the overall chemistry could be characterized using intrinsic acid-base chemistry and the concept of hard/soft Lewis acids/bases. The resulting complex structures were experimentally probed and were found to be in accordance with predictions. For the complexes, the drive toward energy minimization can take several pathways that involve multiple functional groups, thereby leading to a rich chemistry
Long-Term Ageing Studies on Eco-Friendly Resistive Plate Chamber Detectors†
No full textIn high-energy physics, resistive plate chamber (RPC) detectors operating in avalanche mode make use of a high-performance gas mixture. Its main component, Tetrafluoroethane (C2H2F4), is classified as a fluorinated greenhouse gas. The RPC EcoGas@GIF++ collaboration is pursuing an intensive R&D on new gas mixtures for RPCs to explore eco-friendly alternatives complying with recent European regulations. The performance of different RPC detectors has been evaluated at the CERN Gamma Irradiation Facility with Tetrafluoropropene (C3H2F4)-CO2-based gas mixtures. A long-term ageing test campaign was launched in 2022, and since 2023, systematic long-term performance studies have been carried out thanks to dedicated beam tests. The results of these studies are discussed together with their future perspectives
Functional and taxonomic dysbiosis of the supragingival plaque metagenome in Behçet’s disease
No full textBackground: Behçet’s Disease (BD), a complex autoinflammatory disorder, is increasingly linked to microbial dysbiosis, yet the specific microbial signatures and their functional consequences remain incompletely characterized. Elucidating these alterations is crucial for understanding BD pathogenesis. Objective: To identify distinct microbial community structures and functional potentials in supragingival plaque microbiomes of BD patients versus healthy controls (HC) using high-resolution shotgun metagenomic sequencing. Methods: Supragingival plaque from 18 BD patients and 22 HCs was subjected to shotgun metagenomics. Analyses included alpha/beta diversity, taxonomic composition, and MetaCyc pathway abundance, with statistical comparisons. Results: Despite similar age and clinical attachment levels, BD patients exhibited significantly increased alpha diversity and distinct beta diversity compared to HCs. Differential abundance analysis revealed an enrichment of anaerobic and opportunistic taxa in BD (implicating 4 phyla and 28 genera), alongside 19 significantly altered MetaCyc pathways, indicating substantial functional reprogramming within the BD oral microbiome. Conclusion: This high-resolution metagenomic analysis reveals profound oral microbiome dysbiosis in Behçet’s Disease, characterized by altered diversity, a distinct taxonomic signature enriched with pathobionts, and significant functional shifts. These comprehensive microbial alterations are implicated in contributing to the local and systemic inflammatory processes driving BD pathogenesis, offering potential avenues for diagnostic biomarkers and targeted therapies
Rates of Stellar Tidal Disruption Events around Intermediate-mass Black Holes
No full textRates of stellar tidal disruption events (TDEs) around supermassive black holes (SMBHs) have been extensively calculated using the loss cone theory, while theoretical work on TDE rates around intermediate-mass black holes (IMBHs) has been lacking. In this work, we aim to accurately calculate the IMBH TDE rates based on their black hole (BH) masses and the stellar profiles of their host galaxies obtained from the latest observations. We find that the TDE rate per galaxy for IMBHs in the center of small galaxies is similar to that of SMBH TDEs, while the TDE rate per cluster from IMBHs in globular clusters is much lower. Very interestingly, we show that the rate of IMBH TDEs generally increases with the BH mass, which is opposite to the trend seen in SMBH TDEs. As a result, the volumetric TDE rate peaks around a BH mass of 106 M⊙. The IMBH TDEs from galactic nuclei have an overall volumetric rate comparable to SMBH TDEs at ∼10−7 Mpc−3 yr−1, and off-center IMBH TDEs from globular clusters have a volumetric rate that is one or two orders of magnitude lower, assuming that their occupation fraction varies within 10%-100%. Furthermore, we report that IMBH TDEs typically occur in the pinhole regime, which means that deeply plunging events are more likely for IMBH TDEs compared to SMBH TDEs